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Reference
Endpoint:
adsorption / desorption: screening
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2016-04-01 to 2016-04-01
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
EU Method C.19 (Estimation of the Adsorption Coefficient (KOC) on Soil and Sewage Sludge Using High Performance Liquid Chromatography (HPLC))
Deviations:
no
Qualifier:
according to
Guideline:
OECD Guideline 121 (Estimation of the Adsorption Coefficient (Koc) on Soil and on Sewage Sludge using High Performance Liquid Chromatography (HPLC))
Deviations:
no
Qualifier:
according to
Guideline:
other: European Commission (EC), Technical Guidance Document on Risk Assessment Part III, Chapter 4.3: “Use of (Quantitative) Structure Activity Relationships ((Q)SARs) - Soil and Sediment Sorption”, 2003.
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of method:
HPLC estimation method
Media:
other: HPLC column
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- Source and lot/batch No. of test material: I15FB2768
- Expiration date of the lot/batch: 01 July 2017 (retest date)
- Purity: 100% (based on base titration assay)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature
- Stability under test conditions: no data
Radiolabelling:
no
Test temperature:
Column temperature 35°C.
Details on study design: HPLC method:
EQUIPMENT
- Apparatus: Acquity UPLC system (Waters, Milford, MA, USA)
- Type: Acquity UPLC TUV detector (Waters)
- Type, material and dimension of analytical (guard) column: Acquity UPLC HSS Cyano, 100 mm x 2.1 mm i.d., dp = 1.8 µm (Waters)
- Detection: 210 nm (UV)
- Column temperature: 35°C
Flow: 0.4 ml/min
Injection volume: 5 µl

MOBILE PHASES
- Type: 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7
- Solutes for dissolving test and reference substances:
* Solution of the unretained compound:
A 5.0 g/L stock solution of formamide (99.2%, [75-12-7], Alfa Aesar, Karlsruhe, Germany) in methanol was used. The stock solution was diluted to obtain an end solution of 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7.
The formamide blank solution was 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7.
* Reference substance solutions:
Stock solutions of the reference substances at concentrations of approximately 1 g/L in methanol were used. The stock solutions were diluted to obtain an end solution of 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7.
The blank solution for the mixture of reference substances was 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7
* Test solution:
A 1000 mg/L stock solution of the test item was prepared in DMF. The stock solution was diluted 100 times to obtain an end solution of 55/45 (v/v) methanol/0.01 M phosphate buffer pH 7. The final concentration of the test item solution was 10.0 mg/L.
The test item blank solution was DMF 100 times diluted with 55/45 (v/v) methanol/0.01 M phosphate buffer at pH 7.

REFERENCE SUBSTANCES
- Identity: combined reference solution containing Acetanilide, Monuron, 2,5-Dichloroaniline, Napthalene, Benzoic acid phenylester, Fenthion, Phenanthrene and 4,4'-DDT

DETERMINATION OF RETENTION TIMES
- Quantity of test substance introduced in the column: 10 mg/L.
- Quantity of reference substances: 1 g/L in methanol
- Intervals of calibration: no data

REPETITIONS
- Number of determinations: 2 times (test item solution), 1 time (blank solution)

EVALUATION
- Calculation of capacity factors k': from retention time of reference items, the test item, and then on-sorbed chemical item
- Determination of the log Koc value: a correlation of log k' versus log Koc of the reference items is plotted using linear regression - the log k' value of the test item is then used to calculate its log Koc value
Key result
Type:
log Koc
Value:
4.19 dimensionless
pH:
7
Key result
Type:
Koc
Value:
15 000 dimensionless
pH:
7
Details on results (HPLC method):
- Retention times (tr,1 and tr,2) of reference substances used for calibration:
Formamide (t0): tr1 = 0,679 min; tr2= 0,68 min
Acetanilide: tr1 = 0,906 min; tr2= 0,904 min
Monuron: tr1 = 1,135 min; tr2= 1,129 min
2,5-Dichloroaniline: tr1 = 1,306 min; tr2= 1,3 min
Naphthalene: tr1 = 1,544 min; tr2= 1,534 min
Benzoic acid phenylester: tr1 = 1,853 min; tr2= 1,839 min
Fenthion: tr1 = 2,476 min; tr2= 2,452 min
Phenanthrene: tr1 = 2,772 min; tr2= 2,747 min
4,4’-DDT: tr1 = 7,01 min; tr2= 6,919 min

- Details of fitted regression line (log k' vs. log Koc): log k’ = 0.327 x log Koc – 0.810 (r = 0.98, n = 16).
- Average retention data for test substance: 3.14 min

The following pKa values in the logarithm range of 1 - 14 for basic groups in the molecular structure of the test item were calculated using the Perrin calculation method. Based on the calculations, the UPLC analysis was performed at pH 7:

RARN(R1R2) pKa 5.49

RARN(R1R2) pKa 5.10

Validity criteria fulfilled:
yes
Conclusions:
The HPLC method using soil-adsorption-reference data was applied for the determination of the adsorption coefficient (Koc) of JNJ-1806792-AAA (T001325).
Based on pKa calculations, it was concluded that the test item is ionised for at least 10% within pH 5.5 to 7.5. Testing therefore should be performed with both the ionised and non-ionised form according to the guidelines.
Testing with the non-ionised form at pH between 10.9 and 15.2 is technically not possible. The cyanopropyl columns prescribed by the guidelines are not stable outside the pH range 2 to 8. Testing with the ionised form was performed at pH 7.
The Koc and log Koc values of the test item at pH 7 were 15000 and 4.19 respectively.


Description of key information

This endpoint is covered with a GLP-study (Reingruber, 2016) performed according to standard test guideline OECD 121. The mean log Koc of T001325 was determined to be 4.19 using the HPLC estimation method.

Key value for chemical safety assessment

Koc at 20 °C:
15 000

Additional information

[LogKoc: 4.19]